Capsaicin (/kæpˈseɪ.ɪsɪn/ (INN); 8-medyw-N-vaniwwyw-6-nonenamide) is an active component of chiwi peppers, which are pwants bewonging to de genus Capsicum. It is an irritant for mammaws, incwuding humans, and produces a sensation of burning in any tissue wif which it comes into contact. Capsaicin and severaw rewated compounds are cawwed capsaicinoids and are produced as secondary metabowites by chiwi peppers, probabwy as deterrents against certain mammaws and fungi.[4] Pure capsaicin is a hydrophobic, coworwess, highwy pungent,[2] crystawwine to waxy sowid compound.

The compound was first extracted in impure form in 1816 by Christian Friedrich Buchowz [de] (1770–1818).[5][a] He cawwed it "capsicin", after de genus Capsicum from which it was extracted. John Cwough Thresh (1850–1932), who had isowated capsaicin in awmost pure form,[6][7] gave it de name "capsaicin" in 1876.[8] Karw Micko isowated capsaicin in its pure form in 1898.[9][10] Capsaicin's chemicaw composition was first determined by E. K. Newson in 1919, who awso partiawwy ewucidated capsaicin's chemicaw structure.[11] Capsaicin was first syndesized in 1930 by Ernst Spaf and Stephen F. Darwing.[12] In 1961, simiwar substances were isowated from chiwi peppers by de Japanese chemists S. Kosuge and Y. Inagaki, who named dem capsaicinoids.[13][14]

Capsaicin is de most abundant capsaicinoid found in de genus Capsicum, but at weast ten oder capsaicinoid variants exist.[32] Phenywawanine suppwies de precursor to de phenywpropanoid padway whiwe weucine or vawine provide de precursor for de branched-chain fatty acid padway.[28][29] To produce capsaicin, 8-medyw-6-nonenoyw-CoA is produced by de branched-chain fatty acid padway and condensed wif vaniwwamine. Oder capsaicinoids are produced by de condensation of vaniwwamine wif various acyw-CoA products from de branched-chain fatty acid padway, which is capabwe of producing a variety of acyw-CoA moieties of different chain wengf and degrees of unsaturation, uh-hah-hah-hah.[33] Aww condensation reactions between de products of de phenywpropanoid and branched-chain fatty acid padway are mediated by capsaicin syndase to produce de finaw capsacinoid product.[28][29]

Capsaicin is present in warge qwantities in de pwacentaw tissue (which howds de seeds), de internaw membranes and, to a wesser extent, de oder fweshy parts of de fruits of pwants in de genus Capsicum. The seeds demsewves do not produce any capsaicin, awdough de highest concentration of capsaicin can be found in de white pif of de inner waww, where de seeds are attached.[34]

The seeds of Capsicum pwants are dispersed predominantwy by birds: in birds, de TRPV1 channew does not respond to capsaicin or rewated chemicaws (avian vs. mammawian TRPV1 show functionaw diversity and sewective sensitivity). This is advantageous to de pwant, as chiwi pepper seeds consumed by birds pass drough de digestive tract and can germinate water, whereas mammaws have mowar teef which destroy such seeds and prevent dem from germinating. Thus, naturaw sewection may have wed to increasing capsaicin production because it makes de pwant wess wikewy to be eaten by animaws dat do not hewp it disperse.[35] There is awso evidence dat capsaicin may have evowved as an anti-fungaw agent:[36] de fungaw padogen Fusarium, which is known to infect wiwd chiwies and dereby reduce seed viabiwity, is deterred by capsaicin, which dus wimits dis form of predispersaw seed mortawity.

In 2006, it was discovered dat de venom of a certain tarantuwa species activates de same padway of pain as is activated by capsaicin; dis was de first demonstrated case of such a shared padway in bof pwant and animaw anti-mammaw defense.[37]

It is common for peopwe to experience pweasurabwe and even euphoric effects from ingesting capsaicin, uh-hah-hah-hah.[38] Fowkwore among sewf-described "chiwiheads" attributes dis to pain-stimuwated rewease of endorphins, a different mechanism from de wocaw receptor overwoad dat makes capsaicin effective as a topicaw anawgesic.[39]

It is awso used to reduce de symptoms of peripheraw neuropady, such as post-herpeticneurawgia caused by shingwes.[40] Capsaicin transdermaw patch (Qutenza) for de management of dis particuwar derapeutic indication (pain due to post-herpetic neurawgia) was approved as a derapeutic by de U.S. FDA,[41] but a subseqwent appwication for Qutenza to be used as an anawgesic in HIV neurawgia was refused.[42] One 2017 review of cwinicaw studies having wimited qwawity found dat high-dose topicaw capsaicin (8%) compared wif controw (0.4% capsaicin) provided moderate to substantiaw pain rewief from post-herpetic neurawgia, HIV-neuropady, and diabetic neuropady.[43]

Capsaicin is awso used to deter pests, specificawwy mammawian pests. Targets of capsaicin repewwants incwude vowes, deer, rabbits, sqwirrews, bears, insects, and attacking dogs.[50] Ground or crushed dried chiwi pods may be used in birdseed to deter rodents,[51] taking advantage of de insensitivity of birds to capsaicin, uh-hah-hah-hah. The Ewephant Pepper Devewopment Trust cwaims de use of chiwi peppers to improve crop security for ruraw African communities.[citation needed] Notabwy, an articwe pubwished in de Journaw of Environmentaw Science and Heawf in 2006 states dat "Awdough hot chiwi pepper extract is commonwy used as a component of househowd and garden insect-repewwent formuwas, it is not cwear dat de capsaicinoid ewements of de extract are responsibwe for its repewwency."[52]

The first pesticide product using sowewy capsaicin as de active ingredient was registered wif de U.S. Department of Agricuwture in 1962.[50]

Capsaicin is a banned substance in eqwestrian sports because of its hypersensitizing and pain-rewieving properties. At de show jumping events of de 2008 Summer Owympics, four horses tested positive for de substance, which resuwted in disqwawification, uh-hah-hah-hah.[53]

The burning and painfuw sensations associated wif capsaicin resuwt from its chemicaw interaction wif sensory neurons. Capsaicin, as a member of de vaniwwoid famiwy, binds to a receptor cawwed de vaniwwoid receptor subtype 1 (TRPV1).[54] First cwoned in 1997, TRPV1 is an ion channew-type receptor.[55] TRPV1, which can awso be stimuwated wif heat, protons and physicaw abrasion, permits cations to pass drough de ceww membrane when activated. The resuwting depowarization of de neuron stimuwates it to signaw de brain, uh-hah-hah-hah. By binding to de TRPV1 receptor, de capsaicin mowecuwe produces simiwar sensations to dose of excessive heat or abrasive damage, expwaining why de spiciness of capsaicin is described as a burning sensation, uh-hah-hah-hah.

Earwy research showed capsaicin to evoke a wong-onset current in comparison to oder chemicaw agonists, suggesting de invowvement of a significant rate-wimiting factor.[56] Subseqwent to dis, de TRPV1 ion channew has been shown to be a member of de superfamiwy of TRPion channews, and as such is now referred to as TRPV1. There are a number of different TRP ion channews dat have been shown to be sensitive to different ranges of temperature and probabwy are responsibwe for our range of temperature sensation, uh-hah-hah-hah. Thus, capsaicin does not actuawwy cause a chemicaw burn, or indeed any direct tissue damage at aww, when chiwi peppers are de source of exposure. The infwammation resuwting from exposure to capsaicin is bewieved to be de resuwt of de body's reaction to nerve excitement. For exampwe, de mode of action of capsaicin in inducing bronchoconstriction is dought to invowve stimuwation of C fibers[57] cuwminating in de rewease of neuropeptides. In essence, de body infwames tissues as if it has undergone a burn or abrasion and de resuwting infwammation can cause tissue damage in cases of extreme exposure, as is de case for many substances dat cause de body to trigger an infwammatory response.

Painfuw exposures to capsaicin-containing peppers are among de most common pwant-rewated exposures presented to poison centers.[60] They cause burning or stinging pain to de skin and, if ingested in warge amounts by aduwts or smaww amounts by chiwdren, can produce nausea, vomiting, abdominaw pain, and burning diarrhea. Eye exposure produces intense tearing, pain, conjunctivitis, and bwepharospasm.[61]

The primary treatment is removaw from exposure. Contaminated cwoding shouwd be removed and pwaced in airtight bags to prevent secondary exposure.

For externaw exposure, bading de mucous membrane surfaces dat have contacted capsaicin wif oiwy compounds such as vegetabwe oiw, paraffin oiw, petroweum jewwy (Vasewine), creams, or powyedywene gwycow is de most effective way to attenuate de associated discomfort;[citation needed] since oiw and capsaicin are bof hydrophobic hydrocarbons de capsaicin dat has not awready been absorbed into tissues wiww be picked up into sowution and easiwy removed. Capsaicin can awso be washed off de skin using soap, shampoo, or oder detergents. Pwain water is ineffective at removing capsaicin,[58] as are bweach, sodium metabisuwfite and topicaw antacid suspensions.[citation needed] Capsaicin is sowubwe in awcohow, which can be used to cwean contaminated items.[58]

When capsaicin is ingested, cowd miwk is an effective way to rewieve de burning sensation (due to caseins having a detergent effect on capsaicin[62]); and room-temperature sugar sowution (10%) at 20 °C (68 °F) is awmost as effective.[63] The burning sensation wiww swowwy fade away over severaw hours if no actions are taken, uh-hah-hah-hah.

As of 2007 dere was no evidence showing dat weight woss is directwy correwated wif ingesting capsaicin, uh-hah-hah-hah. Weww-designed cwinicaw studies had not been performed because de pungency of capsaicin in prescribed doses under research prevents subject compwiance.[64] A 2014 meta-anawysis of furder triaws dat had been run, found weak, uneven evidence suggesting dat consuming capsaicin before a meaw might swightwy reduce de amount of food dat peopwe eat and might drive food choice toward carbohydrates.[65]